Imaging a

We have imaged lithium-6 thousands of times in an optical tweezer using Λ-enhanced gray molasses cooling light. Despite being the lightest alkali metal, with a recoil temperature of 3.5 µK, we achieve an imaging survival of 0.999 50(2), which sets the new benchmark for low-loss imaging of neutral atoms in optical tweezers. Lithium is loaded directly from a magneto-optical trap into a tweezer with an enhanced loading rate of 0.7. We cool the atom to 70 µK and present a new cooling model that accurately predicts steady-state temperature and scattering rate in the tweezer. These results pave the way for ground state preparation of lithium en route to the assembly of the LiCs molecule in its ground state.

Conformer-Specific Spectroscopy and IR-Induced Isomerization of a Model γ-Peptide: Ac-γ4-Phe-NHMe.

Single-conformation IR and UV spectroscopy of the prototypical capped γ-peptide Ac-γ4-Phe-NHMe (γ4F) was carried out under jet-cooled conditions in the gas phase in order to understand its innate conformational preferences in the absence of a solvent. We obtained conformer-specific IR and UV spectra and compared the results with calculations to make assignments and explore the differences between the γ2- and γ4-substituted molecules. We found four conformers of γ4F in our experiment. Three conformers form nine-membered hydrogen-bonded rings (C9) enclosed by an NH···O═C H-bond but differing in their phenyl ring positions (a, g+, and g-). The fourth conformer forms a strained seven-membered hydrogen-bonded ring in which the amide groups lie in a nominally anti-parallel arrangement stacked on top of one another (labeled S7). This conformer is a close analogue of the amide-stacked conformer (S) found previously in γ2F, in which the Phe side chain is substituted at the γ2 position, Ac-γ2-Phe-NHMe (J. Am. Chem. Soc. 2009, 131, 14243-14245). IR population transfer spectroscopy was used to determine the fractional abundances of the γ4F conformers in the expansion. A combination of force field and density functional theory calculations is used to map out the conformational potential energy surfaces for γ4F and compare it with its γ2F counterpart. Based on this analysis, the phenyl ring prefers to take up structures that facilitate NH···π interactions in γ4F or avoid phenyl interactions with the C═O group in γ2F. The disconnectivity graph for γ4F reveals separate basins associated with the C9 and amide-stacked conformational families, which are separated by a barrier of about 42 kJ/mol. The overall shape of the potential energy surface bears a resemblance to peptides and proteins that have a misfolding pathway that competes with the formation of the native structure.

Spectroscopic Manifestations of Indirect Vibrational State Mixing: Novel Anharmonic Effects on a Prereactive H Atom Transfer Surface.

The NH stretch region of the IR spectrum of methyl anthranilate is modeled in the S1 state to understand the connection between the absence of this fundamental in the fluorescence-dip infrared spectra of Blodgett et al. [Phys. Chem. Chem. Phys. 2020, 22, 14077] and its relevance to the H atom dislocation that occurs upon electronic excitation. A set of coordinates are chosen that highlight the role of certain low-frequency modes. A Hamiltonian is developed in which a large-amplitude two-dimensional surface describing the H-bonded H atom is linearly and quadratically coupled to the remaining degrees of freedom which are treated at the harmonic level. The surface is calculated within the time-dependent density functional theory framework by using the B3LYP/6-311++(d, p) level of theory with dispersion. Our spectral results show that indirect couplings lead to massive intensity sharing over hundreds of wavenumbers. This sharing is predicted to be dramatically reduced upon deuteration. The spectral broadening mechanism is found to involve off-resonant doorway states that are themselves strongly coupled to states nearly degenerate with the NH stretch fundamental and represents a complementary mechanism to previous explanations based on Fermi resonance or the presence of Franck-Condon like combination bands with low-frequency motions. Consistent with the spectra predictions, time-dependent calculations show that if the NH stretch fundamental were excited with an ultrafast laser, it would decay within 40 fs. The competition between H atom dislocation and vibrational relaxation is discussed.

Coexistence of Left- and Right-Handed 12/10-Mixed Helices in Cyclically Constrained ß-Peptides and Directed Formation of Single-Handed Helices upon Site-Specific Methylation.

The inherent conformational preferences of the neutral ß-peptide foldamer series, Ac-(ACHC)n-NHBn, n = 2-4, are studied in the gas phase using conformation-specific IR-UV double resonance methods. The cyclically constrained chiral ß-amino acid cis-2-aminocyclohexane carboxylic acid (ACHC) is designed to bring both right- and left-handed helices into close energetic proximity. Comparison of the infrared spectra in the NH stretch and amide I/II regions with the predictions of DFT calculations lead to the unambiguous assignment of four out of the six observed conformations of the molecules in this series, while corroborating computational and spectral evidence, affords tentative assignments of the remaining two conformers for which IR data were not recorded. The observed structures fall into one of two conformational families: a right-handed 12/10-mixed helix or its "cap-disrupted" left-handed helical analogue, which coexist with significant populations. Site-specific and stereospecific methylation on the cyclohexane backbone at the dipeptide (n = 2) level is also tested as a means to sterically lock in a predetermined cyclohexane chair conformation. These substitutions are proven to be a means of selectively driving formation of one helical screw sense or the other. Calculated relative energies and free energies of all possible structures for the molecules provide strong supporting evidence that the rigid nature of the ACHC residue confers unusual stability to the 12/10-mixed helix conformation, regardless of local environment, temperature, or C-terminal capping unit. The simultaneous presence of both handed helices offers unique opportunities for future studies of their interconversion.

The missing NH stretch fundamental in S1 methyl anthranilate: IR-UV double resonance experiments and local mode theory.

The infrared spectra of jet-cooled methyl anthranilate (MA) and the MA-H2O complex are reported in both S0 and S1 states, recorded using fluorescence-dip infrared (FDIR) spectroscopy under jet-cooled conditions. Using a combination of local mode CH stretch modeling and scaled harmonic vibrational character, a near-complete assignment of the infrared spectra is possible over the 1400-3700 cm-1 region. While the NH stretch fundamentals are easily observed in the S0 spectrum, in the S1 state, the hydrogen bonded NH stretch shift is not readily apparent. Scaled harmonic calculations predict this fundamental at just below 2900 cm-1 with an intensity around 400 km mol-1. However, the experimental spectrum shows no evidence of this transition. A local mode theory is developed in which the NH stretch vibration is treated adiabatically. Minimizing the energy of the corresponding stretch state with one quantum of excitation leads to a dislocation of the H atom where there is equal sharing between N and O atoms. The sharing occurs as a result of significant molecular arrangement due to strong coupling of this NH stretch to other internal degrees of freedom and in particular to the contiguous HNC bend. A two-dimensional model of the coupling between the NH stretch and this bend highlights important nonlinear effects that are not captured by low order vibrational perturbation theory. In particular, the model predicts a dramatic dilution of the NH stretch oscillator strength over many transitions spread over more than 1000 cm-1, making it difficult to observe experimentally.

Vibronic spectroscopy of methyl anthranilate and its water complex: hydrogen atom dislocation in the excited state.

Laser-induced fluorescence (LIF) excitation, dispersed fluorescence (DFL), UV-UV-hole burning, and UV-depletion spectra have been collected on methyl anthranilate (MA, methyl 2-aminobenzoate) and its water-containing complex (MA-H2O), under jet-cooled conditions in the gas phase. As a close structural analog of a sunscreen agent, MA has a strong absorption due to the S0-S1 transition that begins in the UV-A region, with the electronic origin at 28 852 cm-1 (346.6 nm). Unlike most sunscreens that have fast non-radiative pathways back to the ground state, MA fluoresces efficiently, with an excited state lifetime of 27 ns. Relative to methyl benzoate, inter-system crossing to the triplet manifold is shut off in MA by the strong intramolecular NHO[double bond, length as m-dash]C H-bond, which shifts the 3nπ* state well above the 1ππ* S1 state. Single vibronic level DFL spectra are used to obtain a near-complete assignment of the vibronic structure in the excited state. Much of the vibrational structure in the excitation spectrum is Franck-Condon activity due to three in-plane vibrations that modulate the distance between the NH2 and CO2Me groups, ν33 (421 cm-1), ν34 (366 cm-1), and ν36 (179 cm-1). Based on the close correspondence between experiment and theory at the TD-DFT B3LYP-D3BJ/def2TZVP level of theory, the major structural changes associated with electronic excitation are evaluated, leading to the conclusion that the major motion is a reorientation and constriction of the 6-membered H-bonded ring closed by the intramolecular NHO[double bond, length as m-dash]C H-bond. This leads to a shortening of the NHO[double bond, length as m-dash]C H-bond distance from 1.926 Å to 1.723 Å, equivalent to about a 25% reduction in the HO distance compared to full H-atom transfer. As a result, the excited state process near the S1 origin is a hydrogen atom dislocation that is brought about primarily by heavy atom motion, since the shortened H-bond distance results from extensive heavy-atom motion, with only a 0.03 Å increase in the NH bond length relative to its ground state value.

Single-Conformation Spectroscopy of Capped Aminoisobutyric Acid Dipeptides: The Effect of C-Terminal Cap Chromophores on Conformation.

Aminoisobutyric acid (Aib) oligomers are known to form racemic mixtures of enantiomeric left- and right-handed structures. The introduction of a chiral cap converts the enantiomeric structures into diastereomers that, in principle, afford spectroscopic differentiation. Here, we screen different C-terminal caps based on a model Aib dipeptide using double resonance laser spectroscopy in the gas phase to record IR and UV spectra of individual conformations present in the supersonic expansion: NH-benzyl (NHBn) as a reference structure because of its common use as a fluorophore in similar studies, NH- p-fluorobenzyl (NHBn-F), and α-methylbenzylamine (AMBA). For both the NHBn and NHBn-F caps, a single conformer is observed, with infrared spectra assignable to an enantiomeric pair of type II/II' ß-turns in these molecules lacking a chiral center. The higher oscillator strength of the NHBn-F cap enabled UV-UV hole burning, not readily accomplished with the NHBn cap. The AMBA-capped structure, with its chiral center, produced two unique conformers, one of which was a nearly identical left-handed type II ß-turn, while the minor conformer is assigned to a C7-C7 sequential double ring, which is an emergent form of a 27-ribbon. Although not observed, the type II' ß-turn diastereomer, with opposite handedness, is calculated to be 11 kJ/mol higher in energy, a surprisingly large difference. This destabilization is attributed primarily to steric interference between the C-terminal acyl oxygen of the peptide and the chirality-inducing methyl of the AMBA group. Last, computational evidence indicates that the use of an N-terminal aromatic cap hinders the formation of a 310-helix in Ac-Aib2 dipeptides.

Wavepacket insights into the photoprotection mechanism of the UV filter methyl anthranilate.

Meradimate is a broad-spectrum ultraviolet absorber used as a chemical filter in commercial sunscreens. Herein, we explore the ultrafast photodynamics occurring in methyl anthranilate (precursor to Meradimate) immediately after photoexcitation with ultraviolet radiation to understand the mechanisms underpinning Meradimate photoprotection. Using time-resolved photoelectron spectroscopy, signal from the first singlet excited state of methyl anthranilate shows an oscillatory behavior, i.e., quantum beats. Our studies reveal a dependence of the observed beating frequencies on photoexcitation wavelength and photoelectron kinetic energy, unveiling the different Franck-Condon overlaps between the vibrational levels of the ground electronic, first electronic excited, and ground cationic states of methyl anthranilate. By evaluating the behavior of these beats with increasing photon energy, we find evidence for intramolecular vibrational energy redistribution on the first electronic excited state. Such energy redistribution hinders efficient relaxation of the electronic excited state, making methyl anthranilate a poor choice for an efficient, efficacious sunscreen chemical filter.

Conformation-Specific Spectroscopy of Asparagine-Containing Peptides: Influence of Single and Adjacent Asn Residues on Inherent Conformational Preferences.

The infrared and ultraviolet spectra of a series of capped asparagine-containing peptides, Ac-Asn-NHBn, Ac-Ala-Asn-NHBn, and Ac-Asn-Asn-NHBn, have been recorded under jet-cooled conditions in the gas phase in order to probe the influence of the Asn residue, with its -CH2-C(═O)-NH2 side chain, on the local conformational preferences of a peptide backbone. The double-resonance methods of resonant ion-dip infrared (RIDIR) spectroscopy and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used to record single-conformation spectra in the infrared and ultraviolet, respectively, free from interference from other conformations present in the molecular beam. Ac-Asn-NHBn spreads its population over two conformations, both of which are stabilized by a pair of H-bonds that form a bridge between the Asn carboxamide group and the NH and C═O groups on the peptide backbone. In one the peptide backbone engages in a 7-membered H-bonded ring (labeled C7eq), thereby forming an inverse γ-turn, stabilized by a C6/C7 Asn bridge. In the other the Asn carboxamide group forms a C8/C7 H-bonded bridge with the carboxamide group facing in the opposite direction across an extended peptide backbone involving a C5 interaction. Both Ac-Ala-Asn-NHBn and Ac-Asn-Asn-NHBn are found exclusively in a single conformation in which the peptide backbone engages in a type I ß-turn with its C10 H-bond. The Asn residue(s) stabilize this ß-turn via C6 H-bond(s) between the carboxamide C═O group and the same residue's amide NH. These structures are closely analogous to the corresponding structures in Gln-containing peptides studied previously [Walsh, P. S. et al. PCCP 2016, 18, 11306-11322; Walsh, P. S. et al. Angew. Chem. Int. Ed. 2016, 55, 14618-14622], indicating that the Asn and Gln side chains can each configure so as to stabilize the same backbone conformations. Spectroscopic and computational evidence suggest that glutamine is more predisposed than asparagine to ß-turn formation via unusually strong side-chain-backbone hydrogen-bond formation. Further spectral and structural similarities and differences due to the side-chain length difference of these similar amino acids are presented and discussed.

Conformer-Specific and Diastereomer-Specific Spectroscopy of αßα Synthetic Foldamers: Ac-Ala-ßACHC-Ala-NHBn.

The folding propensities of a capped, cyclically constrained, mixed α/ß diastereomer pair, ( SRSS) Ac-Ala-ßACHC-Ala-NHBn (hereafter RS) and ( SSRS) Ac-Ala-ßACHC-Ala-NHBn ( SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/ß-tripeptides contain a cyclohexane ring across each Cα -Cß bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C═O/axial NH or equatorial NH/axial C═O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C═O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/ß-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.

Single Conformation Spectroscopy of Suberoylanilide Hydroxamic Acid: A Molecule Bites Its Tail.

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor that causes growth arrest and differentiation of many tumor types and is an approved drug for the treatment of cancer. The chemical structure of SAHA consists of formanilide "head" and a hydroxamic acid "tail" separated by an n-hexyl chain, C6H5NH(C═O)-(CH2)6-(C═O)NHOH. The alkyl chain's preference for extended structures is in competition with tail-to-head (T-H) or head-to-tail (H-T) hydrogen bonds between the amide and hydroxamic acid groups. Laser desorption was used to bring SAHA into the gas phase and cool it in a supersonic expansion before interrogation with mass-resolved resonant two-photon ionization spectroscopy. Single conformation UV spectra in the S0-S1 region and infrared spectra in the hydride stretch and mid-IR regions were recorded using IR-UV hole-burning and resonant ion-dip infrared spectroscopy, respectively. Three conformers of SAHA were distinguished and spectroscopically characterized. Comparison of the experimental IR spectra with the predictions of density functional theory calculations (DFT, B3LYP D3BJ/6-31+G(d)) leads to assignments for the three conformers, all of which possess tightly folded alkyl chains that enable formation of a T-H (conformer A) or H-T (conformers B and C) hydrogen bonds. A modified version of the generalized Amber force field was developed to more accurately describe the hydroxamic acid OH internal rotor potential, leading to predictions for the relative energies in reasonable agreement with experiment. This force field was used to generate a disconnectivity graph for the low-energy portion of the potential energy landscape of SAHA. This disconnectivity graph contains more than one hundred minima and maps out the lowest-energy pathways between them, which could then be characterized via DFT calculations. This combination of force field and DFT calculations provides insight into the potential energy landscape and how population was funneled into the three observed conformers.

Conformation-specific spectroscopy of capped, gas-phase Aib oligomers: tests of the Aib residue as a 310-helix former.

The conformational preferences of a series of capped peptides containing the helicogenic amino acid aminoisobutyric acid (Aib) (Z-Aib-OH, Z-(Aib)2-OMe, and Z-(Aib)4-OMe) are studied in the gas phase under expansion-cooled conditions. Aib oligomers are known to form 310-helical secondary structures in solution and in the solid phase. However, in the gas phase, accumulation of a macrodipole as the helix grows could inhibit helix stabilization. Implementing single-conformation IR spectroscopy in the NH stretch region, Z-Aib-OH and Z-(Aib)2-OMe are both observed to have minor conformations that exhibit dihedral angles consistent with the 310-helical portion of the Ramachandran map (ϕ, ψ = -57°, -30°), even though they lack sufficient backbone length to form 10-membered rings which are a hallmark of the developed 310-helix. For Z-(Aib)4-OMe three conformers are observed in the gas phase. Single-conformation infrared spectroscopy in both the NH stretch (Amide A) and C[double bond, length as m-dash]O stretch (Amide I) regions identifies the main conformer as an incipient 310-helix, having two free NH groups and two C10 H-bonded NH groups, labeled an F-F-10-10 structure, with a calculated dipole moment of 13.7 D. A second minor conformer has an infrared spectrum characteristic of an F-F-10-7 structure in which the third and fourth Aib residues have ϕ, ψ = 75°, -74° and -52°, 143°, Ramachandran angles which fall outside of the typical range for 310-helices, and a dipole moment that shrinks to 5.4 D. These results show Aib to be a 310-helix former in the gas phase at the earliest stages of oligomer growth.

Inherent Conformational Preferences of Ac-Gln-Gln-NHBn: Sidechain Hydrogen Bonding Supports a ß-Turn in the Gas Phase.

Gas-phase single-conformation spectroscopy is used to study Ac-Gln-Gln-NHBn in order to probe the interplay between sidechain hydrogen bonding and backbone conformational preferences. This small, amide-rich peptide offers many possibilities for backbone-backbone, sidechain-backbone, and sidechain-sidechain interactions. The major conformer observed experimentally features a type-I ß-turn with a canonical 10-membered ring C=O-H-N hydrogen bond between backbone amide groups. In addition, the C=O group of each Gln sidechain participates in a seven-membered ring hydrogen bond with the backbone NH of the same residue. Thus, sidechain hydrogen-bonding potential is satisfied in a manner that is consistent with and stabilizes the ß-turn secondary structure. This turn-forming propensity may be relevant to pathogenic amyloid formation by polyglutamine segments in human proteins.

Ultrasensitive photoreversible molecular sensors of azobenzene-functionalized plasmonic nanoantennas.

This Letter describes an unprecedentedly large and photoreversible localized surface plasmon resonance (LSPR) wavelength shift caused by photoisomerization of azobenzenes attached to gold nanoprisms that act as nanoantennas. The blue light-induced cis to trans azobenzene conformational change occurs in the solid state and controls the optical properties of the nanoprisms shifting their LSPR peak up to 21 nm toward longer wavelengths. This shift is consistent with the increase in thickness of the local dielectric environment (0.6 nm) surrounding the nanoprism and perhaps a contribution from plasmonic energy transfer between the nanoprism and azobenzenes. The effects of the azobenzene conformational change and its photoreversibility were also probed through surface-enhanced Raman spectroscopy (SERS) showing that the electronic interaction between the nanoprisms and bound azobenzenes in their cis conformation significantly enhances the intensity of the Raman bands of the azobenzenes. The SERS data suggests that the isomerization is controlled by first-order kinetics with a rate constant of 1.0 × 10(-4) s(-1). Our demonstration of light-induced photoreversibility of this type of molecular machine is the first-step toward removing present limitations on detection of molecular motion in solid-state devices using LSPR spectroscopy with nanoprisms. Modulating the LSPR peak position and controlling energy transfer across the nanostructure-organic molecule interface are very important for the fabrication of plasmonic-based nanoscale devices.